CA5A p.Leu221=
c.661C>T · rs1597541836 · VCV741579
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00104%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.3 | GERP -4, phastCons 1 |
| Overall | ||
| CADD | 5.662 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00104%
European (non-Finnish) · 12/1,157,498 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000437%
Overall
0.000848%
12/1,414,380 alleles · very rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CA5A
- Protein
- p.Leu221=
- Coding
- c.661C>T
- MANE Select
- NM_001739
- dbSNP
- rs1597541836
- Type
- single nucleotide variant
- Location
- chr16:87891912 (GRCh38)
- Gene constraint
- LOEUF 1.257 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.38
- Residue 221
- the alpha-carbonic anhydrase domain
Similar variants
- CA5A p.Arg32Ter Pathogenic ★★ same type
- CA5A p.Glu241Lys Pathogenic/Likely pathogenic ★★ same type
- CA5A p.Ala149Thr Uncertain significance ★★ ⚠ same type
- CA5A p.Ala208Val Uncertain significance ★★ ⚠ same type
- CA5A p.Ala261Val Uncertain significance ★★ ⚠ same type
- CA5A p.Arg26His Uncertain significance ★★ ⚠ same type
- CA5A p.Asp216Ala Uncertain significance ★★ ⚠ same type
- CA5A p.Gln79Glu Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ca5a-p-leu221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown